福辛普利和缬沙坦对大鼠缺血再灌注模型心肌细胞凋亡的影响

Effects of Fosinopril and Valsartan on cardiomyocyte apoptosis in experimental myocardial Ischemia - reperfusion rats model

目的:观察福辛普利和缬沙坦对大鼠缺血再灌注模型心肌细胞凋亡及凋亡相关蛋白Bcl-2、Bax表达的影响。方法: SD大鼠随机分为四组:假手术组、缺血再灌注组、福辛普利组和缬沙坦组。分别于实验终点采用TUNEL法检测心肌细胞凋亡, 免疫组织化学方法检测心肌组织Bcl-2、Bax蛋白表达。结果:心肌细胞凋亡数目随再灌注时间延长而增加,以缺血30min再灌注48小时最高(247．2±25．9),与缺血30min再灌注4h比较有显著性差异(P<0．01)。福辛普利组与缬沙坦组心肌细胞凋亡数、心肌组织中Bax蛋白表达均低于缺血再灌注组(P<0．05)。结论:心肌缺血再灌注过程中心肌细胞凋亡、心肌组织中Bax蛋白表达是个动态的变化,福辛普利与缬沙坦减少心肌细胞凋亡的数量,其抑制作用可能与部分下调Bax蛋白表达有关。

Objective： To test the effect of fosinopril and valsartan on cardiomyocte apoptosis and expression of Bcl -2 and Bax in myocardium of ischemia- reperfusion （I -R） rat model. Methods： SD rats were randomly divided into four groups as follows ： Sham - operation group, Ischemia - reperfusion group, Fosinopril group and Valsartan group. The TdT - mediated dUTP nick end labeling （TUNEL） method was used to detect apoptotic myocytes in different groups. Bcl- 2 and Bax expression in myocardium were analyzed by immunohistochemical technique. Resuits： The number of apoptotic cardiomytocytes in Ischemia 30min - reperfusion 48 hours group were significantly more （247.2 ± 25.9）, than those in Ischemia 30min - reperfusion 4 hours group （ P 〈 0.01 ）. The number of apoptotic myocytes in Fosinopril group and Valsartan group was less than that of Ischemia - reperfusion group （ P 〈 0.05 ）. The expression of Bax in myocardium was significantly decreased in Fosinopril group and Valsartan group. Conclusion： Ischemia -reperfusion injury could induce myocardial apoptosis, in association with increased expression of Bcl - 2 and Bax. Valsartan could decrease cardiomyocyte apoptosis in the rat hearts after Ischemia - reperfusion, and this decrease was possibly mediated by downregulation of Bax gene expression.